The sex gap in alcohol consumption is closing rapidly, due to alarming increases among women. From 2002-2013, Alcohol Use Disorder (AUD) increased 84% for women, compared to 35% for men. As such, there is an urgent need to determine the factors underlying sex differences in risk for AUD. Current addiction models propose three domains that drive problematic alcohol use and serve as candidate sex-specific risk factors: executive function, negative emotionality, and incentive salience. Data suggest that poor inhibitory control, a key component of executive function, is a stronger risk factor for women than for men. Moreover, there is have preliminary evidence that female drinkers show less engagement of neural inhibitory circuitry, and that this sex difference is influenced by estradiol. However, the degree to which hormonally-moderated sex differences in executive function extend to the negative emotionality and incentive salience domains, and how these sex differences influence current and future drinking is unknown. The goal of this study is to identify the mechanisms underlying sex-specific risk for AUD, and ultimately to help develop sex-specific prevention and treatment efforts. The overall objective of this trial is to determine the neural and hormonal factors contributing to sex-specific risk for AUD in three addiction domains: inhibitory control (executive function), negative emotionality, and alcohol cue reactivity (incentive salience).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
100
Participants will complete three experimental sessions. In each session, participants will provide detailed reports of their alcohol consumption over the past five days, and they will provide a blood sample for hormone assays. They will perform tasks during fMRI to assess each of the neurofunctional addiction domains: inhibitory control, negative emotionality, and cue reactivity. Following the fMRI scan, subjects will self-administer intravenous alcohol to provide a controlled assessment of pharmacologically-driven alcohol consumption.
The Ohio State University
Columbus, Ohio, United States
RECRUITINGNeural inhibitory function
One measure of neural inhibitory function during performance of the stop signal task will be activity (as measured by BOLD % signal change)
Time frame: 13 minutes
Neural inhibitory function
The other measure of neural inhibitory function during performance of the stop signal task will be functional connectivity for the StopInh\>Go contrast.
Time frame: 13 minutes
Neural negative emotionality
One measure of neural negative emotionality during performance of the Emotional Pictures Task will be activity (as measured by BOLD % signal change)
Time frame: 14 minutes
Neural negative emotionality
The other measure of neural negative emotionality during performance of the Emotional Pictures Task will be functional connectivity for the Negative\>Neutral contrast.
Time frame: 14 minutes
Neural alcohol cue reactivity
One measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be activity (as measured by BOLD % signal change)
Time frame: 12 minutes
Neural alcohol cue reactivity
The other measure of neural alcohol cue reactivity during performance of the Alcohol Cue Reactivity Task will be functional connectivity for the Alcohol\>Neutral contrast.
Time frame: 12 minutes
Intravenous alcohol self-administration (IV-ASA)
One measure of IV-ASA will be peak BrAC (mg%; highest BrAC obtained during the IV-ASA period)
Time frame: 60 minutes
Intravenous alcohol self-administration (IV-ASA)
Another measure of IV-ASA will be whether or not a participant reached binge level of alcohol exposure (80mg%)
Time frame: 60 minutes
Intravenous alcohol self-administration (IV-ASA)
The final measure of IV-ASA will be time to reach binge level of alcohol exposure (80mg%)
Time frame: 60 minutes
Self-reported current alcohol consumption
One measure of current alcohol consumption will be number of binge days (4/5 or more drinks in a sitting for women/men) as determined by responses on the Timeline Followback.
Time frame: 20 minutes
Self-reported current alcohol consumption
The other measure of current alcohol consumption will be average peak BrAC obtained on drinking days over the past 5 days, as determined by responses on the Timeline Followback.
Time frame: 20 minutes
Prospective alcohol consumption
One measure of prospective alcohol consumption will be number of binge episodes as determined by responses on the 90-day Timeline Followback.
Time frame: 18 months
Prospective alcohol consumption
The other measure of prospective alcohol consumption will be drinking days per month, as determined by responses on the 90-day Timeline Followback.
Time frame: 18 months
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